The objectives of this research involve the characterization and applications of heme proteins, heme protein microspheres, and synthetic analogs of heme proteins. The reactions of interest include (2) ligand binding to heme proteins and metalloporphyrins, (2) oxygen activation and hydrocarbon oxidation by metalloporphyrins, and (3) the interactions between porphyrins as redox partners in organized media. The heme proteins are relevant to cardiovascular functioning; to drug, hormone, and exobiotic metabolism; to oxidant detoxification and substrate oxidation; and to biological electron transfer and photosynthesis. Some of these studies are directed toward the development of a new class of blood substitutes based on our recent discovery of a simple sonochemical synthesis of hemoglobin (Hb) and other protein microspheres. Other parts of this research provide a fundamental understanding of the molecular mechanisms of heme protein reactions in closely related model metalloporphyrins and oligopeptide-heme complexes. Ultrasonic irradiation of various proteins (e.g., serum albumin and Hb) creates micron-sized spheres that can be either gas-filled or non-aqueous liquid-filled. We have had substantial success in recent development of proteinaceous microspheres as blood substitutes for O2 transport, as contrast agents for magnetic resonance imaging, and as spin-label probes for in vivo O2 and temperature profiling. Microspheres made of Hb and of other protein are currently under development and animal testing as blood substitutes. Other proposed work includes further studies of molecular recognition and substrate specificity on the basis of shape, polarity, charge and hydrogen bonding; the continued examination of oligopeptide-heme complexes as totally synthetic heme proteins; chemical and photochemical generation of highly oxidized iron porphyrin complexes, both in proteins and in synthetic analogs; and the synthesis of bis(porphyrin) metal complexes. In work with synthetic metalloporphyrins and dendrimer- porphyrins, we are developing superstructured macrocycles as shape, size, and polarity selective oxidation catalysts for both hydroxylation and epoxidation. Our exploration of the photochemistry of metalloporphyrins has created a new route to the formation of metal-oxo complexes and other high energy species. As part of this, photo-redox agents have been attached to cytochrome P450 and to porphyrin dimer analogs of the photosynthetic reaction center with the intent of the time resolved observation of intermediates. Continuation of our efforts in these areas should lead (1) to the development of a new class of blood substitutes based on protein microspheres as O2 carriers, (2) to a quantitative understanding of the influences which modulate ligand binding in protein environments, (3) to further characterization and isolation of high oxidation state heme protein intermediates, (4) to a closer understanding of substrate selectivity and regiospecificity by monooxygenases, and (5) to basic knowledge about porphyrin-porphyrin interactions in pi-overlapping systems such as the photosynthetic reaction center.